The present invention relates to a device for packaging a chip shaped carrier having an active surface which is adapted to be read by an electro-optical reading device.
The invention further relates to a process for assembling a plurality of such chip packaging devices.
The invention further relates to a system for carrying out evaluation and/or monitoring methods involving electro-optical reading of an active surface of a chip shaped carrier.
Within the context of the instant invention a chip shaped carrier is a substrate, in particular a glass chip of e.g. squared shape having a thickness of e.g. 0.7 or 1.0 millimeter and a so called active surface, which is a surface coated with an array of different snippets of DNA, e.g. DNA oligonucleotide probes, located at known positions on that surface. Those snippets of DNA serve as probes for detecting DNA fragments with a complementary DNA sequence.
Within the context of the instant invention a packaging device for packaging such a DNA chip is in particular a one-way cartridge made of a plastic material.
DNA chips contained in such cartridges have a wide range of applications. For example, they may be used for understanding the structure-activity relationship between different biological materials or determining the DNA-sequence of an unknown biological material. For instance, the DNA-sequence of such unknown material may be determined by, for example, a process known as sequencing by hybridization. In one method of sequencing by hybridization, a sequences of diverse materials are formed at known locations on a surface of a chip, and a solution containing one or more targets to be sequenced is applied to that surface. The targets will bind or hybridize with only complementary sequences on the substrate. The locations at which hybridization occurs are detected with appropriate detection systems by labeling the targets with a fluorescent dye, radioactive isotope, enzyme, or other marker. Information about target sequences can be extracted from the data obtained by such detection systems.
By combining various available technologies, such as photolithography and fabrication techniques, substantial progress has been made in the fabrication and placement of diverse materials on chips of the above mentioned kind. For example, thousands of different sequences may be fabricated on a single substrate of about 1.28 square centimeter in only a small fraction of the time required by conventional methods. Such improvements make these substrates practical for use in various applications, such as biomedical research, clinical diagnostics, and other industrial markets, as well as the emerging field of genomics, which focuses on determining the relationship between genetic sequences and human physiology.
As commercialization of such chips becomes widespread, an economically feasible and device and a method for packaging the chips with a high-throughput are desired.
Since the active coating of the chip, that is the surface thereof of which is coated with the above mentioned diverse sequences, has to be accessible e.g. to optical detection means, e.g. in the case of fluorescence measurements, the chip has to be inserted into the outer wall of a one-way cartridge, and its active coating faces the interior of the so-called process chamber within the cartridge.
For instance in the above mentioned method of sequencing by hybridization, processing of the active coating of the chip includes flooding of the process chamber of the cartridge with a solution containing one or more targets to be sequenced. Therefore, a liquid-tight connection between the chip and the one-way cartridge is necessary. In a known embodiment described in Specification U.S. Pat. No. 5,945,334 this has been achieved under clean-room conditions by attaching the chip to a cavity of the cartridge by means of an adhesive, that is by gluing it into the cartridge. This known method for connecting the chip to the cartridge has two serious disadvantages. First, the fluorescence of the adhesives used is so high that it substantially interferes and perturbates fluorescence measurements performed on the active coating of the chips and can even have saturating effect on a photomultiplier used for performing the fluorescence measurements. A further disadvantage of the known method for connecting the chip to the cartridge is that it is performed manually and is not suitable for being performed by automated means.
A first aim of the invention is therefore to provide a device for packaging a chip of the above mentioned kind which does not have the above mentioned disadvantages and which provided a liquid-tight connection of such a chip to a cartridge, without using any adhesive substance, the structure of such a device being suitable for automated assembly thereof under clean-room conditions.
A second aim of the invention is to provide a process for assembling a plurality of chip packaging devices according to the invention with a high throughput.
A third aim of the invention is to provide a system for carrying out evaluation and/or monitoring methods involving electro-optical reading of an active surface of a chip shaped carrier without having the above mentioned disadvantages of prior art embodiments.
According to a first aspect of the invention the above mentioned first aim is attained with a device for packaging a chip shaped carrier having an active surface which is adapted to be read by an electro-optical reading device, said device comprising
(a) a cartridge having an opening for introducing a liquid sample into said cartridge said cartridge comprising a casing part,
(b) said casing part having an inner surface and outer surface, a first cavity for receiving a chip shaped carrier, and means which provide visual access to said first cavity, and thereby to said active surface of said chip shaped carrier,
said first cavity having a bottom surface and inclined side wall surfaces which extend between said outer surface of said casing part and said bottom surface and which form an obtuse angle with that bottom surface,
(c) a sealing frame which is part of said casing part and which is made of a compressible material, said sealing frame being connected to said bottom surface of said first cavity, and
(d) a locking frame,
(e) the shape and dimensions of said first cavity said chip shaped carrier, said sealing frame, and said locking frame, being such that
(e.1) said chip shaped carrier fits into the space delimited by said sealing frame, and a gap exists between said sealing frame and the inclined side wall surfaces of said first cavity,
(e.2) said locking frame, is larger than said gap, said locking frame is however insertable into said gap, by pressure exerted on said locking frame against said casing part, said pressure causing a compression of said sealing frame and a corresponding pressure on a substantial part of the outer surface of the lateral periphery of said chip shaped carrier, said outer surface being in contact with said sealing frame.
According to a second aspect of the invention the above mentioned first aim is attained with a device for packaging a chip shaped carrier having an active surface which is adapted to be read by an electro-optical reading device, said device comprising
(a) a cartridge having an opening for introducing a liquid sample into said cartridge, said cartridge comprising a casing part,
(b) said casing part having an inner surface and outer surface, a first cavity for receiving a chip shaped carrier, and means which provide visual access to said first cavity, and thereby to said active surface of said chip shaped carrier,
said first cavity having a bottom surface and inclined side wall surfaces which extend between said inner surface of said casing part and said bottom surface and which form an obtuse angle with that bottom surface,
(c) a sealing frame which is part of said casing part and which is made of a compressible material, said sealing frame being connected to said bottom surface of said first cavity, and
(d) a locking frame,
(e) the shape and dimensions of said first cavity, said chip shaped carrier, said sealing frame, and said locking frame being such that
(e.1) said chip shaped carrier fits into the space delimited by said sealing frame and a gap exists between said sealing frame and the inclined side wall surfaces of said first cavity,
(e.2) said locking frame is larger than said gap, said locking frame is however insertable into said gap by pressure exerted on said locking frame against said casing part, said pressure causing a compression of said sealing frame and a corresponding pressure on a substantial part of the outer surface of the lateral periphery of said chip shaped carrier, said outer surface being in contact with said sealing frame.
The main advantages of a chip packaging device according to the invention are due to the fact that the required liquid-tight connection of the chip to the cartridge is achieved without using any adhesive. These advantages are the absence of perturbating fluorescence related to the means used for making that connection and a longer useful lifetime of unused chips. In addition the coplanar arrangement of the chip and the means for establishing its liquid-tight connection to the cartridge provide improved flow conditions within the process chamber of the cartridge. Moreover, the structure of a chip packaging device according to the invention is suitable for a fully automated, high throughput assembly thereof.
According to the invention the above mentioned second aim is attained with a process for assembling a plurality of chip packaging devices according to the invention, said process comprising
(a) providing a plurality of casing parts and a plurality of said locking frames to an automated assembly line, each of said casing parts comprising a sealing frame,
(b) providing a plurality of chip shaped carriers having each an active surface to said assembly line,
(c) positioning each of said chip shaped carriers within a sealing frame of one of said casing parts by means of a first automatic apparatus,
(d) inserting each of said locking frames into a gap between said sealing frame and inclined side wall surfaces of a first cavity of said casing part by pressing said locking frame against said casing part until the bottom outer surface of said locking frame contacts a bottom surface of said first cavity, the latter inserting and pressing being effected by a second automatic apparatus, and
(e) bonding each of said locking frames onto said bottom surface of said first cavity of said casing part.
The main advantages of a process according to the invention for assembling a plurality of chip packaging devices having the structure proposed by the instant invention are that such a process can be entirely performed using standard automated means and with a high throughput.
According to the invention the above mentioned third aim is attained with a system for carrying out evaluation and/or monitoring methods involving electro-optical reading of an active surface of a chip shaped carrier, said system comprising
(a) a cartridge having an opening for introducing a liquid sample into said cartridge, said cartridge comprising a casing part,
(b) said casing part having an inner surface and outer surface, a first cavity for receiving a chip shaped carrier, and means which provide visual access to said first cavity, and thereby to said active surface of said chip shaped carrier,
said first cavity having a bottom surface and inclined side wall surfaces which extend either between said inner surface of said casing part and said bottom surface or between said inner surface of said casing part and said bottom surface, and which form an obtuse angle with that bottom surface, said bottom surface having an opening which opens into said second cavity,
(c) a sealing frame which is part of said casing part and which is made of a compressible material, said sealing frame being connected to said bottom surface of said first cavity,
(d) a locking frame,
(e) the shape and dimensions of said first cavity, said chip shaped carrier, said sealing frame, said locking frame and said opening of said bottom surface of said first cavity being such that
(e.1) said chip shaped carrier fits into the space delimited by said sealing frame, and a gap exists between said sealing frame and the inclined side wall surfaces of said first cavity,
(e.2) said locking frame is larger than said gap, said locking frame is however insertable into said gap by pressure exerted on said locking frame against said casing part, said pressure causing a compression of said sealing frame and a corresponding pressure on a substantial part of the outer surface of the lateral periphery of said chip shaped carrier, said outer surface being in contact with said sealing frame, and
(f) a chip shaped carrier having an active surface which is adapted to be read by an electro-optical reading device, said chip shaped carrier being positioned in said first cavity of said casing part.
The main advantage of a system according to the invention is that it makes possible to carry out evaluation and/or monitoring methods involving electro-optical readings of an active surface of a chip shaped carrier of the above mentioned type without the above mentioned drawbacks of prior art equipment.